This article reports the synthesis and biological activity of new high affi
nity retinioic acid receptor (RAR) antagonists. The effect of introducing h
eteroatoms in the bicyclic ring system of the potent dihydronaphthalene RAR
antagonist 8, and the variation of the pendant aromatic group on the abili
ty of these compounds to function as RAR antagonists is discussed. The use
of binding, transcriptional, and in vivo assays revealed that the 2,2-dimet
hylthiochromene analogue 59, and the 2,2-dimethylchromene derivative 85, we
re the most effective in blocking retinoid agonist induced activity. (C) 19
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